The present invention relates generally to methods for fabricating micro-tubular, oriented porous polymeric materials, and more particularly to such methods using a phase separation technique carried out with a directional temperature gradient.
Tissue engineering aims at creating biological alternatives to harvested tissues and organs for transplantation. See, for example, Langer, R. and J. Vacanti, “Tissue engineering,” Science 260 (5110): 920-926 (1993). Scaffolding plays a crucial role in the three dimensional neo tissue formation. See, for example, Hubbell, J. A., “Biomaterials in Tissue Engineering,” Bio/Technology 13: 565-576 (1995); Zhang, R. and P. X. Ma, “Synthetic nano-fibrillar extracellular matrices with predesigned macroporous architectures,” Journal of Biomedical Materials Research 52(2): 430-438 (2000); and Ma, P. X. and J. Choi, “Biodegradable polymer scaffolds with well-defined interconnected spherical pore network,” Tissue Engineering, 7(1): 23-33 (2001).
Synthetic biodegradable polymers are attractive candidates for scaffolding fabrication because they do not carry the risk of pathogen transmission and immuno-rejection, and because they degrade and resorb after fulfilling the scaffolding function, therefore eliminating the long-term inflammation and complications associated with foreign body reactions. See, for example, Lu, L., C. A. Garcia and A. G. Mikos, “In vitro degradation of thin poly (D,L-lactic-co-glycolic acid) films,” Journal of Biomedical Materials Research 46 (2): 236-244 (1999); Ma, P. X. and R. Zhang, “Synthetic nano-scale fibrous extracellular matrix,” Journal of Biomedical Materials Research 46(1): 60-72 (1999); Kim, S. S., H. Utsunomiya, J. A. Koski, B. M. Wu, M. J. Cima, J. Sohn, K. Mukai, L. G. Griffith and J. P. Vacanti, “Survival and function of hepatocytes on a novel three-dimensional synthetic biodegradable polymer scaffold with an intrinsic network of channels,” Annals of Surgery 228(1): 8-13 (1998); and Ma, P. X., B. Schloo, D. Mooney and R. Langer, “Development of biomechanical properties and morphogenesis of in vitro tissue engineered cartilage,” Journal of Biomedical Materials Research 29 (12): 1587-1595 (1995).
Each tissue or organ has its characteristic architectural organization, which is closely related to its physiological function. Many organs and tissues have tubular or fibrous bundle architectures. The technology to fabricate single tubular structure at the macro-size scale (a millimeter or larger) such as vascular grafts is available, although the development of perfect vascular grafts is still challenging.
Thus, it would be desirable to provide methods of fabricating polymers into porous materials with non-random, parallel and/or oriented tubular pores throughout the porous materials. It would further be desirable to provide such a method(s) whereby the diameter of the tubules may be controlled from a few to a few hundred micrometers. It would yet further be desirable to provide novel porous materials having oriented micro-tubular architecture, which architecture may advantageously guide cell seeding, distribution, and new tissue formation in vitro and/or in vivo, following the geometrical cues of the micro-tubular architecture in three dimensions. Yet further, it would be desirable to provide such a method(s) wherein the materials may advantageously be natural or synthetic polymers, and/or degradable or non-degradable polymers, and/or blends, mixtures, or composites of polymers.